Fully Synthetic Non-Carbohydrate Heparin Mimetics-Perspectives for Therapeutic Anticoagulation and Beyond?

Abstract

Heparin is one of the oldest drugs on the market. Although clinically well established as an anticoagulant for decades, owing to its natural origin and heterogeneous glycosaminoglycan polysaccharide structure, ensuring consistent quality and reproducible biological activity remains challenging. While these facts argue against future applications of heparin in clinical routine, an increasing number of studies reveal additional potential therapeutic applications of heparin beyond its anticoagulant efficacy, that is, as an antiviral strategy or as a multi-targeted approach in oncology. Therefore, heparin appears to be a structural template for pleiotropic compounds. To combine the beneficial pleiotropic properties of heparin with improved reproducibility and safety, fully synthetic heparin mimetic substances have increasingly become a focus of scientific research. These studies enable more detailed structure-activity relationships of heparin in its interaction with proteins or diseases to be elucidated, thereby facilitating the development of novel compounds for potential therapeutic use. This review focuses in particular on fully synthetic non-carbohydrate heparin mimetic polymers with anticoagulant activities, as well as their properties beyond anticoagulation. Advances in the development of such mimetics, especially over the past decade, allow increasingly robust conclusions to be drawn regarding their efficacy and contribute to a deeper understanding of this class of compounds.